AURORA, Colo. - Researchers, led by scientists at the
University of Colorado School of Medicine, have found basic molecular processes
used by the Zika virus to “hijack” the cells that it infects and potentially
how it makes molecules that are directly linked to disease.
discovery, published in the journal Science, shows that a part of the
Zika virus’s RNA genome folds up into a complex structure and that this
structure leads to the production of smaller RNAs that in related viruses are
directly linked to disease.
cannot reproduce on their own, they must infect cells and “hijack” the cell’s
biological machinery in order to make more copies of themselves. To do this,
viruses use many molecular strategies.
is an example of a virus that does not store its genome in DNA, rather it uses
a related molecule called the viral genomic RNA. Viruses related to Zika, such
as West Nile and Dengue, are known to produce a set of smaller RNAs during
infection (in addition to the long genomic RNA) that have been directly linked
to disease. This process had not been explored with Zika virus until this study.
findings of this study show that Zika infection leads to the production of
these smaller RNAs in several types of cells. The researchers show that part of
the Zika genomic RNA “folds up” into a complex structure that interacts with
and blocks a powerful cellular enzyme that normally destroys RNA, and the
researchers used an advanced technique called x-ray crystallography to solve
the structure of this folded-up RNA segment. By altering the Zika virus genomic
RNA, the team was able to disrupt this structure and eliminate the production
of the potentially disease-causing small RNAs.
Kieft, PhD, professor of biochemistry and molecular genetics, led a team that
consisted of scientists at the University of Colorado School of Medicine
(Aurora, CO), the Advanced Light Source at the Lawrence Berkeley National
Laboratory (Berkeley, CA), and the University of Texas Medical Branch
(Galveston, TX). He is the corresponding author of the article, published in
the journal Science. Benjamin Akiyama, PhD, a member of Dr. Kieft’s Lab,
was the lead author on the study.
first step is stopping any process that causes disease is to understand that
process in detail, preferably at the molecular level.” said Dr. Kieft, who is
also a member of the University of Colorado RNA BioScience Initiative. “Based
on what we knew about related viruses, there was reason to suspect that Zika
virus infection would result in potentially disease-causing RNAs, but we couldn’t
be sure. Now, having observed them and the molecular structures involved, we
can ask new questions about the fundamental molecular processes Zika uses to
take over a cell and cause disease.”
findings could also inform ongoing efforts to develop a vaccine or other
anti-Zika therapeutics. Also, because Zika is closely related to other
dangerous viruses such as Dengue, West Nile, Japanese Encephalitis and Yellow
Fever, the discoveries may be broadly applicable to understanding these viruses
and may help in efforts to stop them.